Summary/Abstract EicOsis is developing a first-in-class analgesic with efficacy against neuropathic pain that will replace and dose spare opioids and thus prevent opioid use disorders (OUDs). The target of the small molecule inhibitor EC5026 is the soluble epoxide hydrolase, a master regulatory enzyme that modulates the activity of endogenous bioactive lipids. The development of EC5026 is currently in progress and progressing to an IND filing and is poised to have a high impact in treating chronic pain in humans. In this proposal we outline aims to reach the next steps in clinical human clinical trials with EC5026 as well as additional preclinical studies to expand the efficacy into models of chronic pain conditions presenting in humans which are most frequently treated with opioids. Additionally, we propose detailed pharmacokinetic, metabolism and distribution studies that will provide the required information for advanced clinical trials examining efficacy in humans. We also propose to optimize a formulation to meet these needs. All of these individual aims are structured to meet 2 year milestones (UG3) and continue to the next planned steps in development (UH3) as these milestones are met. EicOsis is meeting current development goals and EC5026 is well positioned to meet the urgent need of reducing opioid use because even given the updated strategy to treating pain with multimodal approaches, pharmaceuticals are the foundation of treating pain. EC5026 represents a first-in- class analgesic that is not an opioid nor a NSAID but offers effective pain relief for chronic neuropathic pain.